Workers in coke oven plants are exposed to a wide variety of volatile organic compounds and particulates, especially PAHs. The PAHs and their metabolic intermediates might cause damage to the mitochondria . Increasing evidence indicates that PAHs-exposure may relate to mtDNAcn decrease. Ling et al. (2013) observed that decreased sperm mtDNAcn was associated with PAHs-exposure in the male population in Chongqing, China . Pieters et al. (2013) demonstrated that mtDNAcn was inversely associated with indoor PAHs exposure population and their findings were also confirmed in human TK6 cells . Our previous study showed that mtDNAcn had significantly negative correlations with the levels of COE cumulative exposure dose . Moreover, our previous study also found that mtDNAcn had significantly negative correlations with the levels of 1-OHPYR which can be used to estimate the internal exposure of PAHs. In this study, our result showed that male had lower mtDNAcn than female, suggesting that male was susceptibility to PAHs exposure.
GSTT1, GSTM1, and GSTP1 are the important phase II metabolic enzymes in glutathione-S-transferases enzymes system and the genetic polymorphisms in these enzyme genes may alter gene expression levels and its enzymes activity, and subsequently, involve toxicity of PAHs.
The GSTP1 rs1695 is located on exon 5 of chromosome 11q13, and contains a wild-type G allele and mutant A allele. The transition of an A allele to G allele in GSTP1 rs1695 confers increased conjugating activity   and may also with lower levels of genotoxicity in PAHs exposure. Our study found that the 1-OHPYR had an increasing trend with the genotypes AA→AG→GG of GSTP1 rs1695 in the control group. Moreover, our results firstly showed that AA for GSTP1 rs1695 was a risk factor for mtDNAcn in PAHs-exposure. Therefore, we inferred that the toxicity of PAHs may be influenced by GSTP1 rs1695 polymorphisms resulting in the different alteration of mtDNAcn.
Though we also analyzed the association between mtDNAcn and polymorphisms in GSTT1, GSTM1, there was no significant difference. The possible reason is that mitochondrial copy number is affected by many factors, and the polymorphism of the metabolic enzyme gene has a modest effect on mtDNAcn. However, our result showed that the 2-OHNAP and 3-OHPHE in non-deletion for GSTM1 were significantly higher than that in deletion in the exposure group. This confirms that metabolic enzyme gene polymorphism may alter the toxicity of PAHs.
CYP2E1 is an important member of CYP450 system and located on homo sapiens chromosome 10q24.3. The CYP2E1 rs3813867 is a G/C polymorphism located at 1259 position in the 5′-flanking region and the CYP2E1 rs6413432 (T > A) located on intron 6, which can affect the CYP2E1 gene expression level and its enzyme activity . Therefore, polymorphism of CYP2E1 may affect the activity of the enzyme express leading to individual differences in PAHs metabolism. Nan et al. (2001) observed that CYP2E1 polymorphism was an important factor influencing the levels of 1-OHPYR and 2-OHNAP in urinary from coke oven workers . In this study, there was no significant difference between OH-PAHs and CYP2E1 polymorphism, that may be because the PAHs are mostly activated by CYP1A and CYP1B .
Polymorphism of CYP2E1 may also influence the genotoxic of environmental toxins. Guang et al.  found that CYP2E1 rs3813867 mutant allele was associated with higher micronuclei among benzene-exposed shoe workers. Jheneffer et al.  reported that alcoholics who heterozygous in the CYP2E1 rs3813867 showed higher DNA damage (tail length and olive tail moment). Jing et al. found heterozygous in the CYP2E1 rs6413432 had shorter telomere lengths among benzene-exposed shoe workers. However, mtDNAcn change was not associated with CYP2E1 polymorphism in the present study.
In the study, we have analyzed a larger number of samples, which is the advantage of the study. However, several limitations of the present study need to be considered. First, due to the cross-sectional design of this study, a causal relationship between PAHs exposure and mitochondria damage cannot be established. Second, White blood cell differentials and platelet concentrations, which are the major sources of mtDNAcn variability, were not assessed. Third, a large number of studies have shown that there are differences in metabolic enzyme gene polymorphism among different populations. The effects of metabolic enzyme gene polymorphism on mtDNAcn of coke oven workers may not be suitable for all world populations in this study. Hence, further research is needed to address these questions.
In conclusion, the male was susceptibility to PAHs exposure. The AA genotype of GSTP1 rs1695 may influence the toxicity of PAHs and associated with the decreased of mtDNAcn.